DESCRIPTION (Applicant's abstract): This 5-year case control family study of cocaine dependence will examine familial and non-familial antecedents and consequences associated with cocaine dependence. The specific aims of this study are: (i) to examine familial transmission of cocaine dependence and related psychopathology; (ii) to study interrelationships between individual 'and familial factors that are associated with cocaine use, abuse, and dependence; (iii) to specify predisposing factors and outcomes of cocaine use, abuse, and dependence, and their relationship to family factors; and (iv) to compare results of this study with data from a large multi- site family study of alcoholism, the Collaborative Study on the Genetics of Alcoholism (COGA). To accomplish these goals, 500 cocaine dependent subjects in treatment, 500 community-based subjects, and their nearest aged full siblings will be recruited (total of 2000 subjects). Personal interviews will be performed to determine the rates of cocaine use, abuse, and dependence along with alcohol, nicotine, and other substance dependence. In addition, lifetime psychiatric histories will be obtained for major depressive disorder, anxiety disorders, post-traumatic stress disorder, conduct disorder, attention deficit, and hyperactivity. Adverse circumstances including school difficulties, high-risk sexual behaviors, IV drug use violence, and legal difficulties will be assessed. Histories of all first-degree relatives will be obtained from all the subjects. This information will permit analyses of individual and familial factors that are involved in the development of cocaine use, abuse, and dependence, and familial patterns of psychopathology related to cocaine dependence. By surveying groups of high and low risk individuals for the development of cocaine use, abuse, and dependence, the proposed study will generate a unique understanding of the natural history, etiology, and consequences of cocaine dependence in our communities.